Motor Neuron Disease

Currently, I have the pleasure of working with a patient diagnosed with motor neuron disease. This experience has taken me on a journey of what it means to live life every day, and to be thankful for every little win I am awarded. This article is written in thanks.

What is Motor Neuron Disease?

Motor neuron disease is a term that is used to define a group of neurodegenerative diseases, in which motor neurons degenerate, leading to muscle wasting and paralysis. Moreover, when the respiratory muscles are paralysed death can ensue. There are two broad categories of motor neuron disease; sporadic or familial. Sporadic Motor Neuron Disease is not hereditary, and little is known of its exact cause.

What are Motor Neurons?

Motor neurons are nerve cells that carry signals from the brain to the muscles. This being so, they are imperative in controlling the movement of muscle. Unfortunately, neurons are particularly vulnerable to degeneration because they are fixed, post-mitotic (mature) cells, which do not replicate after they are originally formed, and naturally decline in number as we age. This means that if motor neurons die or are damaged for any reason, the body does not have the ability to regenerate them, and cannot recover from this unaided.

Factors Influencing Motor Neuron Disease

There is no single gene mutation or environmental factor that causes motor neuron disease; it is probably caused by a combination of environmental and genetic factors. There is evidence to suggest that 90 percent of cases are influenced by environmental factors including nutrition and exercise, in combination with genes that make people susceptible to the disease.

Familial motor neuron disease is caused by a gene mutation. Therefore, it is hereditary, and can be passed down through the generations. 20 percent of all cases of familial Motor Neuron Disease are caused by a mutation in the gene, SOD1. This mutation has a widespread effect upon motor neurons, creating many problems within the cell that contribute to cell degeneration, death, and ultimately the progression of motor neuron disease.

Protein aggregation is a common cause of neurodegenerative diseases, for example, Alzheimer’s, Huntington’s and Parkinson’s disease. Protein aggregation is considered the aggregation of mis-folded proteins. Hence, there is evidence to suggest that one of the contributing factors to the degeneration of neurons in motor neuron disease is the aggregation of a (mis-folded) mutant SOD1 protein. It is not completely understood how the aggregation of SOD1 proteins contribute to motor neuron disease; however, research has shown that the SOD1 protein can be actively transported into a part of a cell called the endoplasmic reticulum. The endoplasmic reticulum, an organelle (tiny organ) in the cells of your body, plays a major role in the synthesis of proteins and detoxification. Unfortunately, if SOD1 protein is transported into the endoplasmic reticulum it will result in the endoplasmic reticulum becoming stressed, which will eventually lead to apoptosis (programmed cell suicide). This is all happening within the space of one endoplasmic reticulum, of which Two Thousand Six Hundred billion fit onto a 20 cent piece.

SOD1 proteins also aggregate in and on the mitochondria (the powerhouse of a cell), as they are both present in high concentrations in the same place. This leads to an impairment of mitochondrial function, due to SOD1 aggregates blocking the mitochondrial membranes and damaging mitochondrial DNA. Mitochondrial DNA is damaged by reactive oxygen species (only when there is an over-abundance) produced by SOD1. Oxidative damage is thought to be a major contributing factor in the death of motor neurons. For example, reactive oxygen species readily react with lipids, proteins and DNA to induce cellular damage. Moreover, the high metabolic activity of neurons leads to considerable reactive oxygen species formation in these cells. Research shows that the over-expression of a protein used to regulate the transport of SOD1 into mitochondria speeds up motor neuron disease. Moreover, as the mitochondria become overloaded with SOD1, they eventually die.

A recent development into the research on motor neuron disease has identified another protein, TDP-43, that contributes to motor neuron disease when mutated. The mutation causes TDP-43 to aggregate, which leads to apoptosis. However, this is considered a very rare cause of motor neuron disease.

Nutrition and Motor Neuron Disease:

Compromised nutrition leading to weight loss is a common and significant problem in Motor Neuron Disease. The benefit of aggressive and early nutritional therapy can profoundly influence the disease course, quality of life and survival. Inadequate dietary intake can lead to catabolism and atrophy of respiratory muscles, weaken the immune system and contribute to infection.

  1. Vitamin E:

There is evidence to suggest that Vitamin E may have a positive effect on the development of motor neuron disease. However, the research derives from population studies and transgenic mouse models. To date, clinical trials have thus far, failed to show benefits for outcomes of survival, functional status or quality of life.

  1. B Vitamins:

There is some evidence to suggest that patients diagnosed with motor neuron disease have elevated levels of plasma homocysteine. Homocysteine is an excitatory amino acid implicated in many diseases including Motor Neuron Disease. Homocysteine is known to induce apoptotic cell death. Vitamin B12 and Folate are involved in reactions that convert homocysteine to methionine, thereby potentially reducing homocysteine levels. Recent studies undertaken on the relationship between electrical signalling and muscle function has indicated that Motor neuron patients using 25 mg of Vitamin B12 daily by intramuscular injection over a period of 28 days significantly enhanced the functioning of neurons. Nonetheless, it is important to realise that some patients will present as either responders or non-responders to certain types of supplements or medications.

  1.  Zinc:

Zinc is implicated as a supplement with potential benefit given its role in the function of SOD 1. In transgenic models of Motor Neuron Disease, it has been shown, that mutant forms of SOD 1 have an impaired ability to bind to zinc and thus toxicity was heightened. Research has shown that zinc supplementation can up-regulate metallothioneins (cysteine rich agents capable of binding heavy metals), and facilitate antioxidant function. Moreover, zinc acts to block glutamate (a primary excitatory neurotransmitter in the central nervous system, that in excess may be responsible for nerve damage) release, enhanced reuptake, and protect cells against the damaging effects of excessive glutamate. This being so, one could also consider the use of melatonin given its ability to attenuate glutamate-induced cell death in motor neuron cells. Hence, oxidative damage may be significantly reduced. In a motor neuron population using 300 mg/day of melatonin (by rectal suppository for 24 month) melatonin was shown to significantly attenuate oxidative damage.

  1. Genistein:

Genistein is a phytoestrogen. Oestrogen compounds have been implicated as neuro-protective agents promoting survival of motor neurons. Survival differences between male and female SOD 1 transgenic mice have been attributed to the role of oestrogen. It is suggested that 16mg/kg twice daily in transgenic male mice pose a gender specific neuro-protective function that is not shown in transgenic female mice.

  1. Creatine:

At the time of writing this article there has been no clinical trials that have shown any significant effect on grip strength, and energy metabolism in motor neuron populations.

  1. Coenzyme Q10:

Individuals diagnosed with sporadic Motor Neuron Disease display significantly higher levels of oxidized CoQ10. Oxidised CoQ10 can generate superoxide and hydrogen peroxide, agents capable of inducing an increase in reactive oxygen species. Patients diagnosed with Sporadic Motor Neuron disease using 3000 mg of CoQ10 daily combined with 300 IU of Vitamin E had a significant decline in hydrogen peroxide.

  1. L-Carnitine:

Early oral administration of L-Carnitine has been shown to significantly delay symptom onset, prolong motor function and extend survival in SOD 1 transgenic mice.

There may be potential in aggressive nutritional therapy, either in isolation or alongside enteral nutrition in the management of motor neuron disease. If you have any questions regarding this post or would like to pose a question please write to Appointments can be made by contacting 0432234822.

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